This project seeks to understand the neural substrates involved in implicit associative processes through the imaging (fMRI) of drug-relevant memory associations. Complex associative learning and memory processes influenced by reinforced drug use experiences result in neurobiological consequences that include the strengthening of motivationally-relevant associative memories, which, in turn, affect subsequent drug use behavior outside conscious awareness. These drug-related associative effects have been shown to consistently correlate with and predict level of drug use. The application of associative memory concepts from basic science research suggests that one's behavior at any moment is governed primarily by the current pattern of activation in memory, and that activation is often primarily an implicit, or relatively automatic process. To observe differences in neural activity of drug-relevant associative effects, the proposed project will involve a between subjects comparison of marijuana dependent individuals and a group of healthy controls during performance on a marijuana-Implicit Association Test (IAT). In addition, a within subjects comparison will provide information relevant to the neural activation of memory associations on compatible and incompatible trials of the IAT to help determine neural correlates of the IAT effect. The proposed work is the first study to observe differences in neural activity between marijuana dependent individuals and non-users on an indirect test of associations. Indirect assessments of drug-relevant associations, like the IAT, are rooted in associative learning principles, with associative strength being a key determinant of information processing expressed as memory biases that influence behavior. By eliciting activation of associative drug-relevant memories through performance on this indirect test, it is possible to increase our understanding of individual differences in associative structures that influence drug use behavior outside of conscious awareness. The proposed fMRI project will complement and extend findings derived through behavioral measures. This is a step toward the use of multiple methods to investigate and increase our understanding of implicit processes and their regulatory influence on addictive behaviors. Addiction is a progressive, relapsing condition and once established, it is difficult to overcome without continual intervention. If understanding the neural mechanisms involved in these under-studied but influential implicit processes helps to expand our knowledge of influences affecting continued drug abuse, then this work is indeed significant. Understanding neural mediators of behavior like drug-related implicit associations can help in the development of risk reduction and treatment intervention components to improve the efficacy of current protocol. PUBLIC HEALTH RELEVANCE: This project seeks to understand the neural substrates involved in implicit associative processes through the imaging of drug-relevant memory associations that have been shown to consistently correlate with and predict levels of drug use. To observe neural activity, the project involves functional imaging (fMRI) of marijuana associations during performance on the Implicit Association Test (IAT) among marijuana dependent individuals and a comparison group of healthy controls. By eliciting activation of associative drug-relevant memories through performance on this indirect test of association, it may be possible to increase our understanding of individual differences in associative structures that influence drug use behavior outside of conscious awareness.